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Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment
Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.ORCID-id: 0000-0002-6097-6318
Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden..
Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden..
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2017 (Engelska)Ingår i: Criminology & Public Policy, ISSN 1538-6473, E-ISSN 1745-9133, Vol. 19, nr 3, s. 205-213Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, and neutrophil degranulation is a major response to bacterial infections.

OBJECTIVES: To assess the value of plasma calprotectin as an early marker of bacterial infections in critically ill patients and compare it with the corresponding values for procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC).

METHODS: We measured daily plasma calprotectin levels in 110 intensive care unit patients using a newly developed turbidimetric assay run on clinical chemistry analysers. The likelihood of infection was determined according to the International Sepsis Forum criteria.

RESULTS: Overall, 58 patients (52.7%) developed a suspected or confirmed bacterial infection. Plasma calprotectin predicted such infections within 24 hours with an area under the receiver operating characteristics curve (ROC area) of 0.78 (95% CI, 0.68-0.89). The ROC area for calprotectin was significantly greater than the corresponding ROC areas for WBC (P < 0.001) and PCT (P = 0.02) but only marginally better than the ROC area for CRP (0.71; 95% CI, 0.68-0.89).

CONCLUSION: Plasma calprotectin appears to be a useful early marker of bacterial infections in critically ill patients, with better predictive characteristics than WBC and PCT.

Ort, förlag, år, upplaga, sidor
2017. Vol. 19, nr 3, s. 205-213
Nationell ämneskategori
Anestesi och intensivvård
Identifikatorer
URN: urn:nbn:se:uu:diva-329205ISI: 000408400800003PubMedID: 28866970OAI: oai:DiVA.org:uu-329205DiVA, id: diva2:1141241
Tillgänglig från: 2017-09-14 Skapad: 2017-09-14 Senast uppdaterad: 2021-03-09Bibliografiskt granskad
Ingår i avhandling
1. Avian antibodies applied in particle enhanced turbidimetric immunoassay: Developement of serum/plasma calprotectin immunoassay and its clinical performance as a marker for bacterial infections
Öppna denna publikation i ny flik eller fönster >>Avian antibodies applied in particle enhanced turbidimetric immunoassay: Developement of serum/plasma calprotectin immunoassay and its clinical performance as a marker for bacterial infections
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Calprotectin is a cytosolic protein in the granulocytes, consisting of S100A8 and S100A9. On the site of inflammation, the neutrophils release the cytosol as an inflammatory response. The circulating calprotectin concentration increases and can therefore be used as marker for neutrophil activation and inflammation.

To raise specific antibodies, it is crucial to immunize with pure calprotectin antigen. We purified calprotectin from human granulocytes by ion-exchange chromatography, dialysed it towards saline and concentrated it to required levels, suited for immunisation of the hens. The purified antigen solutions were assigned concentration values by the Biuret method and the purity was checked by SDS PAGE and size exclusion chromatography. The yield was approximately 2 mg purified antigens per unit of 450 ml blood.

A prototype calprotectin particle enhanced turbidimetric immunoassay was developed from the purified antigen and the affinity purified antibodies. The antigen was spiked into PBS to prepare calibrators and controls. The antibodies were coated to latex particles to prepare immunoparticles. The performance of the immunoassay was technically tested on a clinical chemistry analyser. LoQ, antigen excess, linearity, precision and calibration stability met the pre-set criteria.

In the production process of immunoparticles there are several factors affecting the performance of the assay. Investigating eight factors applying a Taguchi L12 screening, we experienced that conductivity and pH of conjugate buffer, coating grade and conductivity of dialysis buffer II affected the sensitivity and antigen excess the most.

The assay was used to measure clinical samples. Serum samples from elderly people aged 70+ were collected. Only patients with no infections were included to establish a reference interval for this patient group. The reference interval in serum was 0.3 mg/L to 2.5 mg/L for both genders. Furthermore, the plasma calprotectin immunoassay was tested clinically on critically ill patients to assess the ability of plasma calprotectin as an early marker for detection of bacterial infections. It showed promising results. Calprotectin was a better predictive marker for sepsis than procalcitonin and white blood cell count. Because some patients with an inflammation have low numbers of granulocytes, we examined the correlation between white blood cell count and the calprotectin levels in a group of patients with an inflammation. There was a weak correlation between the number of white blood cells and calprotectin concentration.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2018. s. 54
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1507
Nyckelord
Sepsis, avian antibodies, calprotectin antigen, particle enhanced turbidimetric immunoassay.
Nationell ämneskategori
Klinisk laboratoriemedicin
Forskningsämne
Klinisk kemi
Identifikatorer
urn:nbn:se:uu:diva-363261 (URN)978-91-513-0480-9 (ISBN)
Disputation
2018-12-06, Robergssalen, ingång 40, Akademiska Sjukhuset,, Uppsala, 10:00 (Norska)
Opponent
Handledare
Forskningsfinansiär
Norges forskningsråd, 223022/O30
Tillgänglig från: 2018-11-15 Skapad: 2018-10-15 Senast uppdaterad: 2018-11-30

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Nilsen, TomLarsson, Anders

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